Q54273635
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The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.
Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.
- MeSH
- antigen AC133 imunologie MeSH
- imunokonjugáty farmakologie MeSH
- kolorektální nádory farmakoterapie imunologie patologie MeSH
- kopolymer kyseliny glykolové a mléčné chemie MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- monoklonální protilátky chemie MeSH
- nanočástice aplikace a dávkování chemie MeSH
- nosiče léků chemie MeSH
- oxaliplatin chemie MeSH
- protinádorové látky chemie MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice.
- MeSH
- apoptóza účinky léků MeSH
- autofagie * účinky léků MeSH
- biologické markery metabolismus MeSH
- biologické modely MeSH
- lidé MeSH
- sodíko-draslíková ATPasa metabolismus MeSH
- srdeční glykosidy farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Cardiac glycosides are bioactive natural compounds well-known mainly for their potency to induce a cardiotonic effect by sodium-potassium ATPase inhibition. For many years, cardiac glycosides have been utilized to treat heart failure and arrhythmias; however, according to novel research studies, these compounds have an enormous potential also as medicinally promising compounds for cancer treatment. The goal of this review is to provide a brief insight into the research topic of cardiac glycosides by describing their chemical structure, biosynthesis, the mechanism of action, anticancer potential alongside with the most significant clinical trials, as well as their other biological activities, such as the modulation of the immune system.
Sesquiterpene lactones are bioactive natural compounds with anticancer, antiprotozoal, immunomodulatory, antibacterial and antiviral activity which have potential for drug development. The aim of this review article is to provide a brief insight into the field of sesquiterpene lactones: the main mechanisms of their biological actions, as well as particular compounds, are described, some of which have already become a basis of a drug development and are being tested in clinical trials.
- MeSH
- artemisininy MeSH
- etnofarmakologie MeSH
- farmakognozie MeSH
- fytogenní protinádorové látky izolace a purifikace MeSH
- imunomodulace MeSH
- inhibitory enzymů MeSH
- laktony * farmakokinetika farmakologie terapeutické užití MeSH
- seskviterpeny guajanové farmakokinetika farmakologie terapeutické užití MeSH
- seskviterpeny farmakokinetika farmakologie terapeutické užití MeSH
- Tanacetum parthenium chemie MeSH
- thapsigargin MeSH
- Publikační typ
- práce podpořená grantem MeSH
Surface-modified gold multibranched nanoparticles (AuMs) were prepared by simple chemical reduction of gold chloride aqueous solution followed by in situ modification by using water-soluble arenediazonium tosylates with different functional organic groups. Chemical and morphological structures of the prepared nanoparticles were examined by using transmission electron and scanning electron microscopies. The covalent grafting of organic compounds was confirmed by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and Raman spectroscopy techniques. Covalent functionalization of nanoparticles significantly expands the range of their potential uses under physiological conditions, compared with traditional non-covalent or thiol-based approaches. The antibacterial effect of the surface-modified AuMs was evaluated by using Escherichia coli and Staphylococcus epidermidis bacteria under IR light illumination and without external triggering. Strong plasmon resonance on the AuMs cups leads to significant reduction of the light power needed kill bacteria under the mild conditions of continuous illumination. The effect of the surface-modified AuMs on the light-induced antibacterial activities was founded to be dependent on the grafted organic functional groups.
